Biology of chronic graft-versus-host disease: implications for a future therapeutic approach.

Martin, Paul J (2008) Biology of chronic graft-versus-host disease: implications for a future therapeutic approach. The Keio journal of medicine, 57 (4). pp. 177-183. ISSN 1880-1293

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Abstract

Hematopoietic cell transplantation (HCT) is frequently complicated by graft-versus-host disease (GVHD). During the past three decades, experimental studies and clinical observations have elucidated the pathophysiology of acute GVHD, but the biology of chronic GVHD is much less well understood. Recommendations of the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD have begun to standardize the diagnosis and clinical assessment of the disease. These criteria have emphasized the importance of qualitative differences, as opposed to time of onset after HCT, in making the distinction between acute and chronic GVHD. Experimental studies have generated at least four theories to explain the pathophysiology of chronic GVHD. These theories include 1) thymic damage and defective negative selection of T cells generated from marrow progenitors after HCT, 2) aberrant production of transforming growth factor-beta, 3) auto-antibody production, and 4) deficiency of T-regulatory cells. Recent studies in humans have corroborated a possible role for each of these mechanisms in humans. No animal model fully replicates all of the features of chronic GVHD in humans, and it appears likely that multiple biological mechanisms account for the diverse features the disease. Chronic GVHD may represent a "syndrome" with diverse causes among individual patients. In the future, it might become possible to tailor specific therapeutic interventions for patients as individually needed for each distinct pathophysiologic mechanism involved in development of the disease.

Item Type:	Article or Abstract
Additional Information:	This article is freely available at the URL above
PubMed ID:	19110529
NIHMSID:	NIHMS132355
PMCID:	PMC2722785
Grant Numbers:	R01 CA098906-06
Keywords or MeSH Headings:	Animals; B-Lymphocytes/physiology; CD4-Positive T-Lymphocytes/physiology; Chronic Disease; Disease Models, Animal; Graft vs Host Disease/etiology/immunology/therapy; Humans; T-Lymphocytes, Regulatory/physiology; Transforming Growth Factor beta/physiology;
Subjects:	Diseases > Graft vs Host
Depositing User:	Library Staff
Date Deposited:	28 Jul 2009 16:36
Last Modified:	14 Feb 2012 14:42
URI:	http://authors.fhcrc.org/id/eprint/315

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